MAP2K4
MAP2K4 is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response.
Overview
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signalling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3.
CIViC holds 2 clinical evidence items and 0 assertions across 2 variants, naming Selumetinib and PLX8725. Open Targets scores its association with cancer at 0.77 (direct and indirect evidence; datatypes literature 0.95, animal model 0.27, genetic association 0.29, somatic mutation 0.97). IntOGen calls it a driver in 15 cohorts (4 activating, 11 loss-of-function), covering Invasive Breast Carcinoma, Cholangiocarcinoma, Colorectal Adenocarcinoma, Oesophagogastric Adenocarcinoma, Oesophageal Squamous Cell Carcinoma, Hepatocellular Carcinoma and others.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · MAP2K4 is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response.
- 1 · What it is
MAP2K4 is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response.
- 2 · What goes wrong in cancer
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signalling pathway.
- 3 · How drugs use it
No product in this corpus aims at MAP2K4 yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
External identifiers
Sources: HGNC HGNC:6844 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P45985 (protein name, function text, keywords and locations (REST API)); CIViC gene MAP2K4 (2 evidence items, 0 assertions, 2 variants; diseases: Cancer, Uterus Leiomyosarcoma (GraphQL API, CC0)); Open Targets ENSG00000065559 (association with cancer (MONDO_0004992) 0.77; per-cancer scores at or above 0.5: melanoma 0.51, skin cancer 0.52, breast cancer 0.72, biliary tract cancer 0.50 (GraphQL API, CC0)); IntOGen MAP2K4 (driver in 15 cohorts (Act 4, LoF 11); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signalling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to pro-inflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. Location: Cytoplasm; Nucleus (UniProt). Locus 17p12 (HGNC).
- Breast cancer: Open Targets association 0.72 with breast cancer (MONDO_0007254); IntOGen driver in 6 cohorts (BRCA)
- Colorectal cancer: IntOGen driver in 3 cohorts (COADREAD)
- Pancreatic ductal adenocarcinoma: IntOGen driver in 2 cohorts (PAAD, PANCREAS)
- Gastric & gastro-oesophageal junction cancer: IntOGen driver in 1 cohort (EGC)
- Oesophageal cancer: IntOGen driver in 1 cohort (ESCC)
- Hepatocellular carcinoma: IntOGen driver in 1 cohort (HCC)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 2 therapies; IntOGen calls it an activating (Act) driver in 4 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 11 cohorts; CIViC holds 2 clinical evidence items on its variants. Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Uterus Leiomyosarcoma.
Latest papers
topQuery for this target: (TITLE:"MAP2K4" OR ABSTRACT:"MAP2K4" OR TITLE:"mitogen-activated protein kinase kinase 4" OR ABSTRACT:"mitogen-activated protein kinase kinase 4" OR TITLE:"Dual specificity mitogen-activated protein kinase kinase 4" OR ABSTRACT:"Dual specificity mitogen-activated protein kinase kinase 4" OR TITLE:"MEK4" OR ABSTRACT:"MEK4" OR TITLE:"JNKK1" OR ABSTRACT:"JNKK1" OR TITLE:"PRKMK4" OR ABSTRACT:"PRKMK4") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about MAP2K4, not a curated reading list.
Similar pages
not linked directly; found by shared links- TargetCDH11
Shares Biliary tract cancer (all types), Skin cancer (all types), Oesophageal cancer, Hepatocellular carcinoma.
- TargetFOXP1
Shares Biliary tract cancer (all types), Skin cancer (all types), Oesophageal cancer, Breast cancer (all types).
- TargetARID2
Shares Biliary tract cancer (all types), Skin cancer (all types), Oesophageal cancer, Hepatocellular carcinoma.
- TargetBAP1
Shares Biliary tract cancer (all types), Oesophageal cancer, Hepatocellular carcinoma, Breast cancer (all types).
- TargetPBRM1
Shares Biliary tract cancer (all types), Skin cancer (all types), Oesophageal cancer, CIViC.
- TargetFGFR4
Shares Biliary tract cancer (all types), Hepatocellular carcinoma, Breast cancer (all types), CIViC.
- TargetPALB2
Shares Biliary tract cancer (all types), Breast cancer (all types), CIViC, IntOGen.
- TargetGRIN2A
Shares Biliary tract cancer (all types), Skin cancer (all types), Breast cancer (all types), IntOGen.